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https://www.readbyqxmd.com/read/29027583/changes-in-circulating-cell-free-dna-and-nucleosomes-in-patients-with-exacerbated-psoriasis
#1
Martin Beranek, Zdenek Fiala, Jan Kremlacek, Ctirad Andrys, Jan Krejsek, Kvetoslava Hamakova, Marcela Chmelarova, Vladimir Palicka, Lenka Borska
Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6...
October 13, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28986368/chromosome-1q21-3-amplification-is-linked-to-breast-cancer-recurrence
#2
(no author information available yet)
The 1q21.3 amplification can be detected in cfDNA from most patients with recurrent breast cancer.
October 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#3
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28982650/incidental-detection-of-maternal-neoplasia-in-noninvasive-prenatal-testing
#4
Nilesh G Dharajiya, Daniel S Grosu, Daniel H Farkas, Ron M McCullough, Eyad Almasri, Youting Sun, Sung K Kim, Taylor J Jensen, Juan-Sebastian Saldivar, Eric J Topol, Dirk van den Boom, Mathias Ehrich
BACKGROUND: Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA)(5) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy...
October 5, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28978556/genomic-heterogeneity-as-a-barrier-to-precision-medicine-in-gastroesophageal-adenocarcinoma
#5
Eirini Pectasides, Matthew D Stachler, Sarah Derks, Yang Liu, Steven Maron, Mirazul Islam, Lindsay Alpert, Heewon Kwak, Hedy Kindler, Blase Polite, Manish R Sharma, Kenisha Allen, Emily O'Day, Samantha Lomnicki, Melissa Maranto, Rajani Kanteti, Carrie Fitzpatrick, Christopher Weber, Namrata Setia, Shu-Yuan Xiao, John Hart, Rebecca Nagy, Kyoung-Mee Kim, Min-Gew Choi, Byung Hoon Min, Katie S Nason, Lea O'Keefe, Masayuki Watanabe, Hideo Baba, Rick Lanman, Agoston T Agoston, David J Oh, Andrew Dunford, Aaron R Thorner, Matthew D Ducar, Bruce M Wollison, Haley A Coleman, Yuan Ji, Mitchell C Posner, Kevin K Roggin, Kiran Turaga, Paul Chang, Kyle Hogarth, Uzma Siddiqui, Andres Gelrud, Gavin Ha, Samuel S Freeman, Justin Rhoades, Sarah Reed, Greg Gydush, Denisse Rotem, Jon Davison, Yu Imamura, Viktor Adalsteinsson, Jeeyun Lee, Adam J Bass, Daniel V Catenacci
Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumor. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations...
October 4, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28978004/detection-of-esr1-mutations-in-circulating-cell-free-dna-from-patients-with-metastatic-breast-cancer-treated-with-palbociclib-and-letrozole
#6
Rekha Gyanchandani, Karthik J Kota, Amruth R Jonnalagadda, Tanya Minteer, Beth A Knapick, Steffi Oesterreich, Adam M Brufsky, Adrian V Lee, Shannon L Puhalla
ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973495/identification-of-mutations-in-cell-free-circulating-tumor-dna-in-adrenocortical-carcinoma-a-case-series
#7
Sara G Creemers, Esther Korpershoek, Peggy N Atmodimedjo, Winand N M Dinjens, Peter M van Koetsveld, Richard A Feelders, Leo J Hofland
Context: The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices on diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA (ctDNA) predicted tumor dynamics. Case descriptions: This pilot study included six patients. Next-generation sequencing (NGS) showed mutations in 3 ACCs. From these patients, blood was drawn before (1-2 weeks) and after surgery, from which cell-free circulating DNA (cfDNA) was isolated...
June 30, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28969034/dynamics-of-egfr-mutations-in-plasma-recapitulates-the-clinical-response-to-egfr-tkis-in-nsclc-patients
#8
Liwen Xiong, Shaohua Cui, Jingyan Ding, Yun Sun, Longfu Zhang, Yizhuo Zhao, Aiqin Gu, Tianqing Chu, Huimin Wang, Hua Zhong, Xin Ye, Yi Gu, Xin Zhang, Min Hu, Liyan Jiang
OBJECTIVES: Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. PATIENTS AND METHODS: Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967919/chromosome-1q21-3-amplification-is-a-trackable-biomarker-and-actionable-target-for-breast-cancer-recurrence
#9
Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz, Siti Maryam J M Yatim, Puay Leng Lee, Yi Bao, Tse Hui Lim, Panpan Wang, Wai Leong Tam, Annette R Kodahl, Maria B Lyng, Suman Sarma, Selena Y Lin, Alexander Lezhava, Yoon Sim Yap, Alvin S T Lim, Dave S B Hoon, Henrik J Ditzel, Soo Chin Lee, Ern Yu Tan, Qiang Yu
Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence...
September 25, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28954786/a-phase-1-dose-escalation-study-of-oral-asp8273-in-patients-with-non-small-cell-lung-cancers-with-epidermal-growth-factor-receptor-mutations
#10
Helena Yu, Alexander I Spira, Leora Horn, Jared Weiss, Howard West, Giuseppe Giaccone, Tracey L Evans, Ronan J Kelly, Bhardwai B Desai, Andrew Krivoshik, Diarmuid Moran, Srinivasu Poondru, Fei Jie, Kouji Aoyama, Anne Keating, Geoffrey R Oxnard
PURPOSE: Acquired EGFR T790M mutations are the most frequently identified resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant lung cancers. ASP8273 is a third-generation EGFR TKI with antitumor activity in preclinical models of EGFR-mutant lung cancer that targets mutant EGFR, including EGFR T790M. EXPERIMENTAL DESIGN: In this multi-cohort, phase 1 study (NCT02113813), escalating doses of ASP8273 (25-500mg) were administered once daily to non-small cell lung cancer (NSCLC) patients with disease progression after prior treatment with an EGFR TKI...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28951314/longitudinal-cell-free-dna-analysis-in-patients-with-small-cell-lung-cancer-reveals-dynamic-insights-into-treatment-efficacy-and-disease-relapse
#11
Karinna Almodovar, Wade T Iams, Catherine B Meador, Zhiguo Zhao, Sally York, Leora Horn, Yingjun Yan, Jennifer Hernandez, Heidi Chen, Yu Shyr, Lee P Lim, Christopher K Raymond, Christine M Lovly
INTRODUCTION: Patients with small cell lung cancer (SCLC) have a poor prognosis and limited treatment options. Since access to longitudinal tumor samples is very limited in patients with this disease, we chose to focus our studies on the characterization of plasma cell-free DNA (cfDNA) for rapid, noninvasive monitoring of disease burden. METHODS: We developed a liquid biopsy assay that quantifies somatic variants in cfDNA. The assay detects single nucleotide variants, copy number alterations, and insertions or deletions in 14 genes that are frequently mutated in SCLC, including TP53, RB1, BRAF, KIT, NOTCH1-4, PIK3CA, PTEN, FGFR1, MYC, MYCL1, and MYCN...
September 22, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28949453/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#12
(no author information available yet)
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28948585/-innovative-prenatal-testing-clinical-applications-and-ethical-considerations
#13
Mei-Chih Huang, Shio-Jean Lin, Chih-Ling Chen, Tzu-Jung Huang
The biomedical technology related to prenatal screen/diagnosis has developed rapidly in recent decades. Many prenatal genetic examinations are now available to assist pregnant women to better understand the status and development of their fetus. Moreover, many commercial advertisements for innovative prenatal examinations are now shown in the media. Cell-free DNA Screening (cfDNA screening), a non-invasive prenatal testing (NIPT) procedure, is a safe and high accuracy test that may be done at an earlier gestational age to screen for fetal aneuploidy...
October 2017: Hu Li za Zhi the Journal of Nursing
https://www.readbyqxmd.com/read/28947568/discrimination-of-germline-egfr-t790m-mutations-in-plasma-cell-free-dna-allows-study-of-prevalence-across-31-414-cancer-patients
#14
Yuebi Hu, Ryan S Alden, Justin I Odegaard, Stephen R Fairclough, Ruthia Chen, Jennifer Heng, Nora Feeney, Rebecca Nagy, Jayshree Shah, Bryan Ulrich, Martin Gutierrez, Richard B Lanman, Judy E Garber, Cloud P Paweletz, Geoffrey R Oxnard
PURPOSE: Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline risk alleles. We studied EGFR T790M mutations in non-small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. EXPERIMENTAL DESIGN: Patients with EGFR-mutant NSCLC, some with known germline EGFR T790M, underwent plasma genotyping. Separately, deidentified genomic data and buffy coat specimens from a clinical plasma next-generation sequencing (NGS) laboratory were reviewed and tested...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28945480/myriad-applications-of-circulating-cell-free-dna-in-precision-organ-transplant-monitoring
#15
Philip Burnham, Kiran Khush, Iwijn De Vlaminck
Solid organ transplantation remains the preferred treatment for many end-stage organ diseases, but complications due to acute rejection and infection occur frequently and undermine its long-term benefits. Monitoring of the health of the allograft is therefore a critically important component of post-transplant therapy. Here, we review several emerging applications of circulating cell-free DNA (cfDNA) in the post-transplant monitoring of rejection, infection, and immunosuppression. We further discuss the cellular origins and salient biophysical properties of cfDNA...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28940814/preanalytical-blood-sample-workup-for-cell-free-dna-analysis-using-droplet-digital-pcr-for-future-molecular-cancer-diagnostics
#16
Joost H van Ginkel, Daan A van den Broek, Joyce van Kuik, Dorothé Linders, Roel de Weger, Stefan M Willems, Manon M H Huibers
In current molecular cancer diagnostics, using blood samples of cancer patients for the detection of genetic alterations in plasma (cell-free) circulating tumor DNA (ctDNA) is an emerging practice. Since ctDNA levels in blood are low, highly sensitive Droplet Digital PCR (ddPCR) can be used for detecting rare mutational targets. In order to perform ddPCR on blood samples, a standardized procedure for processing and analyzing blood samples is necessary to facilitate implementation into clinical practice. Therefore, we assessed the technical sample workup procedure for ddPCR on blood plasma samples...
September 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28925570/first-trimester-screening-based-on-ultrasound-and-cfdna-vs-first-trimester-combined-screening-a-randomized-controlled-study
#17
Karl Oliver Kagan, Fabrina Sroka, Jiri Sonek, Harald Abele, Kai Lüthgens, Maximilian Schmid, Philipp Wagner, Sara Brucker, Diethelm Wallwiener, Markus Hoopmann
OBJECTIVE: Prospective randomized trial to compare the performance of first trimester combined screening (FTCS) with an approach that uses the combination of a detailed ultrasound examination and cfDNA analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks' gestation (fetal NT ≤3.5 mm and no fetal defects) were randomized into two groups. In the first group, the risk of aneuploidy was assessed using FTCS based on the most recent FMF UK algorithm...
September 19, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#18
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
October 2017: Cell Research
https://www.readbyqxmd.com/read/28915599/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#19
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911154/prognostic-significance-of-circulating-ret-m918t-mutated-tumor-dna-in-patients-with-advanced-medullary-thyroid-carcinoma
#20
Gilbert J Cote, Caitlin Evers, Mimi I Hu, Elizabeth G Grubbs, Michelle D Williams, Tao Hai, Dzifa Y Duose, Michal R Houston, Jacquelin H Bui, Meenakshi Mehrotra, Steven G Waguespack, Naifa L Busaidy, Maria E Cabanillas, Mouhammed Amir Habra, Rajyalakshmi Luthra, Steven I Sherman
Context: Interpretation of calcitonin measurement to predict the prognosis of medullary thyroid carcinoma (MTC) requires multiple measurements over an extended time period, making it an imperfect biomarker for evaluating prognosis or disease behavior. Single circulating cell-free DNA (cfDNA) values have been shown to be a valuable prognostic marker for several solid tumors. Objective: We tested the hypothesis that cfDNA containing the RET M918T mutation could be detected in the blood of patients with advanced MTC whose tumor harbored an M918T mutation and would be able to predict overall survival more reliably than calcitonin...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
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